An estimated 6 million units of RBCs are transfused each year in sub-Saharan Africa with over 80% of these dedicated to the treatment of severe malaria anemia in children. Children are especially susceptible to malaria and suffer a case fatality rate that is 20 fold higher than adults. Three features relevant to this project have emerged from prior studies of acute Plasmodium falciparum malaria in children. First, profound anemia is a common manifestation of severe malaria occurring in up to two-thirds of those with any form of severe malaria syndrome. Secondly, lactic acidosis accompanies severe malaria anemia and is a strong predictor of fatal outcome. Thirdly, small studies have suggested that RBC transfusion is highly effective to reverse lactic acidosis in children with malaria and severe anemia. It is currently not known if blood storage, as practice worldwide, results in impairment of the ability of RBCs to delivery oxygen to tissues. Recent retrospective studies in non-malarial regions of the world, studying cohorts of patients very different from childhood malaria, have proposed limiting the allowable storage duration of RBCs. Such limitations would place further constraints on the available blood supply with serious consequences for the size of the national blood inventories throughout sub-Saharan Africa. Application of such inventory restrictions in the absence of data related to transfusion for malaria is unwarranted. This project seeks to study the effect of the transfusion of RBCs of different storage periods on tissue oxygenation among children with severe malaria anemia in Uganda. Children with severe anemia and elevated blood lactate levels will receive RBC transfusion according to their usual care. Either short-storage or long-storage RBCs will be selected for transfusion. The primary measurement will be the decline in lactate levels that accompany transfusion. The study is designed to determine whether or not prolonged storage age RBCs are at least 75% as effective as short-storage RBCs for relief of lactic acidosis. The results of the study should be of direct bearing to the care of millions of children with malaria, and of direct value to policy makers establishing limits for blood storage worldwide. PUBLIC HEALTH RELEVANCE: This project is relevant to: 1) millions of children worldwide who receive RBC transfusions for treatment of severe malaria anemia (SMA). Worldwide, SMA is one of the leading reasons for RBC transfusion. The results of the study will allow blood establishments serving malaria areas to understand the proper duration of blood storage for transfusion. 2) millions of RBC transfusion recipients in wealth nations. The results of this study will document, using a physiologic endpoint, whether or not prolonged-storage age blood performs as well as short-duration stored blood. The results will have direct bearing on decisions regarding the shelf-life of blood worldwide.